Maternal genetic polymorphisms of phase II metabolic enzymes and the risk of fetal neural tube defects

Abstract

Background: Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with the risk of fetal neural tube defects (NTDs). Whether maternal genetic variants related to PAH metabolism contribute to the development of fetal NTDs remains unclear. Methods: We conducted a case-control study in a Chinese population to examine the association of selected maternal genetic variants of phase II enzymes involved in the elimination of the metabolic intermediates of these chemicals with fetal NTD risk, and to evaluate possible interaction of the genetic variant and maternal exposure to indoor air pollution from coal combustion and smoking (IAPCC). Blood samples were collected from 534 NTD case mothers and 534 control mothers and assayed for 12 polymorphisms of 5 genes encoding phase II enzymes. Results: We found that the rs9282861 GG genotype of SULT1A1 was associated with an elevated risk of total NTDs (odds ratio [OR] 5 2.12, 95% confidence interval [CI]: 1.49-3.00), compared with the GA genotype. The SULT1A1 rs9282861 variant showed a significant additive interaction with maternal exposure to IAPCC for NTD risk, with a relative excess risk of interaction of 1.20 (95% CI 0.23-2.18), and the OR for the joint effect of high-level IAPCC exposure and the GG genotype was 8.37 (95% CI: 3.63-19.28). Conclusion: Maternal SULT1A1 polymorphism is associated with the risk of fetal NTDs, and has an additive-scale interaction with maternal IAPCC exposure for NTD risk.Birth Defects Research (Part A) 100:13-21, 2014.

Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans

“…Most nonsyndromic spina bifida is thought to be of multifactorial origin [ 151 ] with influence of both genetic and environmental factors [ 144 , 152 ]. Among the environmental factors associated with increased risk of spina bifida are increased pregnancy weight [ 153 – 158 ], maternal smoking [ 159 – 161 ], drug intake specifically of antiepileptic drugs [ 162 – 164 ], and maternal illnesses such as diabetes [ 165 , 166 ] and hyperthermia [ 167 ]. Dietary factors including water chlorination [ 168 – 170 ], inositol intake [ 171 ], simple sugar intake [ 172 ], and the intake of trace elements and other micronutrients [ 173 – 176 ] have been proposed to act as either contributory or preventive factors for spina bifida.…”

Association between maternal single nucleotide polymorphisms in genes regulating glucose metabolism and risk for neural tube defects in offspring

“…The study subjects were from an ongoing case‐control study performed in five rural counties (Pingding, Xiyang, Taigu, Zezhou, Shouyang) of Shanxi Province in northern China, where a population‐based birth defects surveillance program has been established (Liu et al, ; Wang et al, ). Birthing hospitals report to the birth defects information system with cases of major birth defects and fetuses that are terminated due to prenatal diagnosis.…”

Risk of congenital heart diseases associated with NAT2 genetic polymorphisms and maternal polycyclic aromatic hydrocarbons exposure

“…Given interindividual differences in the ability of the xenobiotic metabolism, variation within key genes may disturb metabolism pathway and form DNA and protein adducts in fetal tissues, which in turn could affect fetal development. Current evidence suggests that susceptibility gene displays a significant interaction with environmental pollutants in regard to risks for birth defects (eg, spina bifida and orofacial cleft) …”